Home Blog of Signal Transduction NF-κB HDAC Zearalenone induces mitochondria-associated endoplasmic reticulum membranes dysfunction in piglet Sertoli cells based on endoplasmic reticulum stress

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Zearalenone induces mitochondria-associated endoplasmic reticulum membranes dysfunction in piglet Sertoli cells based on endoplasmic reticulum stress

Zearalenone (ZEA) is an estrogen-like mycotoxin, which mainly led to reproductive toxicity. The study aimed to investigate the molecular mechanism of ZEA-induced dysfunction of mitochondria-associated endoplasmic reticulum membranes (MAM) in piglet Sertoli cells (SCs) via the endoplasmic reticulum stress (ERS) pathway. In this study, SCs were used as a research object that was exposed to ZEA, and ERS inhibitor 4-Phenylbutyrate acid (4-PBA) was used as a reference. The results showed that ZEA damaged cell viability and increased Ca2+ levels; damaged the structure of MAM; up-regulated the relative mRNA and protein expression of glucose-regulated protein 75 (Grp75) and mitochondrial Rho-GTPase 1 (Miro1), while inositol 1,4,5-trisphosphate receptor (IP3R), voltage-dependent anion channel 1 (VDAC1), mitofusin2 (Mfn2) and phosphofurin acidic cluster protein 2 (PACS2) were down-regulated. After a 3 h 4-PBA-pretreatment, ZEA was added for mixed culture. The results of 4-PBA pretreatment showed that inhibition of ERS reduced the cytotoxicity of ZEA against piglet SCs. Compared with the ZEA group, inhibition of ERS increased cell viability and decreased Ca2+ levels; restored the structural damage of MAM; down-regulated the relative mRNA and protein expression of Grp75 and Miro1; and up-regulated the relative mRNA and protein expression of IP3R, VDAC1, Mfn2, and PACS2. In conclusion, ZEA can induce MAM dysfunction in piglet SCs via the ERS pathway, whereas ER can regulate mitochondria through MAM.

 

Comments：

The study investigated the molecular mechanism of Zearalenone (ZEA) induced dysfunction of mitochondria-associated endoplasmic reticulum membranes (MAM) in piglet Sertoli cells (SCs) through the endoplasmic reticulum stress (ERS) pathway. The results showed that ZEA exposure damaged the cell viability and MAM structure, increased Ca2+ levels, and up-regulated the relative mRNA and protein expression of Grp75 and Miro1, while down-regulated IP3R, VDAC1, Mfn2, and PACS2. However, pretreatment with the ERS inhibitor 4-PBA reduced the cytotoxicity of ZEA against piglet SCs, restored the MAM structure, and regulated the expression of Grp75, Miro1, IP3R, VDAC1, Mfn2, and PACS2.

The study suggests that ZEA-induced ERS pathway can lead to MAM dysfunction in piglet SCs, and ER can regulate mitochondria through MAM. The findings may provide insights into the toxic effects of ZEA on reproductive health and the potential use of ERS inhibitors in reducing ZEA-induced toxicity. However, further studies are needed to explore the specific molecular mechanisms and potential therapeutic strategies for ZEA-induced reproductive toxicity.

Related Products

Cat.No. Product Name Information
S4125 4-PBA (Sodium Phenylbutyrate) 4-PBA (Sodium Phenylbutyrate) is a salt of 4-phenylbutyrate (4-PBA) or 4-phenylbutyric acid.Sodium phenylbutyrate is a histone deacetylase inhibitor, used to treat urea cycle disorders.

Related Targets

HDAC